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Type 2 diabetes mellitus (T2DM) is the cause of the development of diabetic nephropathy — a complication that determines the high degree of disability and mortality of such patients. Until recently, approaches to normalizing glucose levels did not have a significant possibility of influencing the outcome of kidney damage in diabetes. Type 2 sodium glucose cotransporter inhibitors (SGLT2) are a new class of glucose-lowering drugs that improve glycemic control due to an insulin-independent mechanism of action associated with increased urinary glucose excretion. The review provides an analysis of the results of studies on the assessment of nephroprotective actions — one of the pleiotropic actions of this drugs group. These materials show the properties of SGLT2 inhibitors to reduce the risk of developing and the progression of albuminuria, to save glomerular filtration rate, to reduce the frequency of end-stage renal disease and the need for renal replacement therapy in patients with T2DM. The article gives and analyzes the currently existing hypotheses of the mechanism of action of these glucose-lowering drugs. The risk of the most common renal complications with the use of SGLT2 inhibitors is considered. The practical aspects of the use of SGLT2 inhibitors in modern algorithms for the care of patients with T2DM are indicated, as well as the prospects for new randomized clinical trials.

Military Medical Academy of S.M. Kirov, Saint-Petersburg, Russia Recent clinical trials about the cardiovascular safety of empagliflozin and liraglutide demonstrated a convincing lowering effect on mortality from cardiovascular causes among the patients with type 2 diabetes. These findings resulted in many questions about why this phenomenon was seen in two drugs with widely different mechanisms of functioning. It is important to note that the glucose-lowering effect was moderate, although a feature seen in both empagliflozin and liraglutide was their ability to increase insulin sensitivity. In many fundamental studies, this feature was associated with a reduction of cardiovascular risks. Insulin resistance, which has always been a pathophysiological base for the development of cardiovascular disease in patients with type 2 diabetes, is a topic for this report. Different methods to manage insulin resistance, including lifestyle changes, drug treatment and metabolic surgery, are discussed. Furthermore, the most common features of glucose-lowering drugs are analysed, including protective effects for cardiovascular outcomes in patients with type 2 diabetes presented in randomised clinical trials. Studies include the United Kingdom Prospective Diabetes Study (UKPDS), PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive), Insulin Resistance Intervention After Stroke (IRIS), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) and the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). The current study shows that the potential to reduce the risk of cardiovascular disease is determined not only by effective lowering of glucose but also by the ability to lower insulin resistance, which causes a paradigm shift in the management of type 2 diabetes.